Migration of T cells in vivo: Molecular mechanisms and clinical implications

T cells play an important role In the pathogenesis of chronic and autoimmun e Inflammatory diseases. They are found in high numbers in involved tissues , such as the lamina propria of the gut in patients with Crohn disease. Mod ifying T-cell number and function may therefore be of therapeutic value. In principle, two mechanisms may be responsible for the development of such T-cell Infiltrates: 1) an increased rate of T-cell immigration into involv ed tissues or 2) an increased proliferation rate, decreased T-cell death (a poptosis) rate, and prolonged retention of T cells already in the tissue. B ased on the theory that T cells selectively target affected tissues through organ-specific adhesion-molecule pathways, current anti-adhesion-molecule therapy aims to interfere selectively with T-cell entry to stop tissue dama ge. However, the traffic of labeled T cells in unmanipulated animals shows that the entry of T-cell subsets into tissues is not organ-specific, even under conditions of differing adhesion molecule and chemokine receptor expressio n. In contrast, within various tissues, both movement and survival of T-cel l subsets differ considerably. These observations suggest that the differen tial expression of adhesion molecules and chemokine receptors on T cells se rves at least two functions in vivo. First, during migration of T cells out of the bloodstream, the different adhesion-molecule pathways provide redun dancy, which guarantees that T-cell subsets are able to enter the different tissues in sufficient numbers (security). Second, adhesion molecules and c hemokine receptors mediate T-cell interactions within the tissue that are c haracteristic for each subset and each microenvironment and determine the n ature of the ensuing immune response (selectivity). Shifting the focus of a nti-adhesion-molecule therapy toward the T cells in diseased tissue may lea d to new treatment options.